By "maximally tolerated" pentobarbital dosing, daily, for five weeks, we have developed a quantitatively defined and reproducible barbiturate dependency cat model to use as a control. 1. Against this reference, effects of low chronic dose, and of frequency and duration of exposure to barbiturates will be investigated in relation to (a) tolerance characteristics, and (b) withdrawal sign intensities. 2. Phenobarbital induced dependency will be compared by pharmacologically defined criteria, with the control pentobarbital and barbital dependencies. 3. The cat model system will provide the basis for a meaningful evaluation of withdrawal treatments. The effective uses of the benzodiazepines (diazepam and chlordiazepoxide) will be compared to that of the established phenobarbital treatment. 4. Pharmacokinetics of benzodiazepines will be defined for their parent drugs and active metabolites to provide the rationale for a chronic dosing regimen for future study. 5. Effects of phenytoin during withdrawal will be explored further by EEGs taken from different loci in the brain with permanently implanted electrodes. Barbiturate withdrawal seizures might prove useful as an epilepsy model. 6. Neurophysiologic alterations during withdrawal will be examined; their neuronal loci and mechanisms will be further investigated utilizing extra- and intracellular microelectrode recording techniques in spinal segmental reflex pathways. 7. After establishing low-level pentobarbital dependency, the sleep study will be continued. The effects of low-level chronic dosing will be compared with those produced by "maximally tolerable" dosing. BIBLIOGRAPHIC REFERENCES: Boisse, N.R. and Okamoto, M., Physical dependency to barbital compared to pentobarbital: Part I "Chronically equivalent dosing method. J. Pharmacol. Exp. Ther. (1977, accepted) in press. Boisse, N.R. and Okamoto, M., Physical dependency to barbital compared to pentobarbital: Part II. Tolerance characteristics. J. Pharmacol. Exp. Ther. (1977, accepted) in press.